Whooping cough, or pertussis, is a severe infectious human respiratory tract disease brought about by Bordatella pertussis. The disease typically manifests itself in children and immunization is accomplished by initial vaccination of children in their infancy followed by repeated vaccination during the early years of their childhood.
Historically, pertussis vaccines in the art were prepared using whole-cell heat-killed bacteria. The use of these vaccines, however, had a number of drawbacks in administration and in the adverse side effects that resulted from their administration. Over time, health care administrators attributed a decrease in the administration rate of pertussis vaccines and a corresponding increase in the incidence of whooping cough in children to these drawbacks.
More recently, researchers have developed acellular vaccines which have been proven to have milder side effects. The central component of these recently developed vaccine strains is the pertussis toxin. According to methods now known in the art, prior to use, the pertussis toxin is detoxified by either chemical detoxification or by recombinant production of genetically detoxified toxin containing mutations for several different variations that produce the detoxified toxin. See, e.g., U.S. Pat. No. 5,785,971, issued to R. Rappuoli, et al., U.S. Pat. No. 5,733,600 issued to W. N. Burnette; and, EPO Publication No. EP 0 396 964 B1, in the name of Pizza, et al.
While the administration drawbacks of pertussis vaccines of the past have been overcome by the development and introduction of acellular vaccines, problems associated with producing sufficient quantities of these vaccines remain. The pertussis toxin is a complex multi-component antigen that is made up of five sub-units, S1–S5. The difficulties in large quantity production of the toxin are several. The bacterium conventionally used to produce the toxin is difficult to grow and grows slowly. It does not reliably produce the toxin in large quantities when grown in culture. Moreover, the toxin produced by the bacterium is difficult to purify from its most significant contaminant, filamentous hemagglutinin. Thus, presently, there is no vaccine production strain that produces assembled pertussis toxin with high yield and purity and which grows rapidly and reliably. Nor is there one that produces such a pertussis toxin that is substantially, if not totally, free of filamentous hemagglutinin.